Within 24 h of systemic delivery, melatonin reduces STAT3 phosphorylation—thereby dismantling the immunosuppressive IL-10/VEGF loop that nurtures tumour immune evasion—and diminishes HIF-1α accumulation in tumour-associated macrophages (TAMs), tipping their transcriptional programme from an arginase-1/VEGF-rich M2 phenotype toward an iNOS/IL-12-high M1 state (43, 44). Here, NOS2 is linked to neoplasm.